A potential new recombinant echovirus 18 strain detected in a 4-year-old child with encephalitis in China in 2019


The species Enterovirus B includes diverse serotypes that can cause a wide spectrum of human diseases, such as aseptic encephalitis, myocarditis, and paralysis. In this study, a 4-year-old child was diagnosed with viral encephalitis, but the causative agent could not be identified using routine immunological tests. Using metagenomic RNA sequencing, a novel strain of enterovirus B, strain PC06, was identified, and its genome sequence was determined by RT-PCR and Sanger sequencing. The viral genome sequence was most similar to that of echovirus E18 strain E18-HeB15-54498/HeB/CHN/2015 (GenBank accession MG720261), with 87.73% nucleotide sequence identity, while the viral proteins shared 96.98% amino acid sequence identity with those of E18 strain Jena/AN1365/10 (GenBank accession no. KX139452). Phylogenetic analysis based on the VP1 and 3D genes revealed discrepant placement of PC06 in the two trees. In the 3D tree, PC06 formed a separate branch together with other recombinant E18 strains. Further recombination tests revealed that PC06 had possibly undergone recombination at a site between the structural and non-structural regions during its evolutionary history. Based on the analysis of VP1 phylogeny and using online genotyping tools, this potential recombinant is tentatively considered a strain of echovirus 18. This information might contribute to the diagnosis and prevention of related diseases.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


  1. 1.

    Tapparel C, Siegrist F, Petty TJ, Kaiser L (2013) Picornavirus and enterovirus diversity with associated human diseases. Infect Genet Evol 14:282–293

    Article  Google Scholar 

  2. 2.

    Chen B-S, Lee H-C, Lee K-M, Gong Y-N, Shih S-R (2020) Enterovirus and encephalitis. Front Microbiol 11:261

    Article  Google Scholar 

  3. 3.

    Huang H-I, Shih S-R (2015) Neurotropic enterovirus infections in the central nervous system. Viruses 7:6051–6066

    CAS  Article  Google Scholar 

  4. 4.

    Lindberg AM, Andersson P, Savolainen C, Mulders MN, Hovi T (2003) Evolution of the genome of Human enterovirus B: incongruence between phylogenies of the VP1 and 3CD regions indicates frequent recombination within the species. J Gen Virol 84:1223–1235

    CAS  Article  Google Scholar 

  5. 5.

    Oberste MS, Maher K, Pallansch MA (2004) Evidence for frequent recombination within species human enterovirus B based on complete genomic sequences of all thirty-seven serotypes. J Virol 78:855–867

    CAS  Article  Google Scholar 

  6. 6.

    Kroneman A, Vennema H, Deforche K, Avoort H, Peñaranda S, Oberste M, Vinjé J, Koopmans M (2011) An automated genotyping tool for enteroviruses and noroviruses. J Clin Virol 51:121–125

    CAS  Article  Google Scholar 

  7. 7.

    Lukashev AN, Lashkevich VA, Ivanova OE, Koroleva GA, Hinkkanen AE, Ilonen J (2005) Recombination in circulating Human enterovirus B: independent evolution of structural and non-structural genome regions. J Gen Virol 86:3281–3290

    CAS  Article  Google Scholar 

  8. 8.

    Gray LD, Fedorko D (1992) Laboratory diagnosis of bacterial meningitis. Clin Microbiol Rev 5:130–145

    CAS  Article  Google Scholar 

  9. 9.

    Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120

    CAS  Article  Google Scholar 

  10. 10.

    Li D, Liu C-M, Luo R, Sadakane K, Lam T-W (2015) MEGAHIT: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph. Bioinformatics 31:1674–1676

    CAS  Article  Google Scholar 

  11. 11.

    Buchfink B, Xie C, Huson DH (2015) Fast and sensitive protein alignment using DIAMOND. Nat Methods 12:59–60

    CAS  Article  Google Scholar 

  12. 12.

    Sun G, Yi M, Tian H, Shao C, Yang S, Han J, Wang X, Wang Y, Shen Q, Wang H (2014) A novel human enterovirus recombinant from a child with diarrhea. Adv Virol 159:333–337

    CAS  Google Scholar 

  13. 13.

    Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874

    CAS  Article  Google Scholar 

  14. 14.

    Guindon S, Dufayard J-F, Lefort V, Anisimova M, Hordijk W, Gascuel O (2010) New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 59:307–321

    CAS  Article  Google Scholar 

  15. 15.

    Martin DP, Murrell B, Golden M, Khoosal A, Muhire B (2015) RDP4: Detection and analysis of recombination patterns in virus genomes. Virus Evol 2015:1

    Google Scholar 

  16. 16.

    Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC (1999) Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 73:152–160

    CAS  Article  Google Scholar 

  17. 17.

    Tyler KL (2018) Acute viral encephalitis. N Engl J Med 379:557–566

    Article  Google Scholar 

  18. 18.

    Singh TD, Fugate JE, Rabinstein AA (2015) The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology 84:359–366

    CAS  Article  Google Scholar 

  19. 19.

    Kennedy PG, Quan P-L, Lipkin WI (2017) Viral encephalitis of unknown cause: current perspective and recent advances. Viruses 9:138

    Article  Google Scholar 

  20. 20.

    Miao Z, Yan J, Sun Y, Chen Y, Gong L, Ge Q, Shi W, Pan J, Mao H, Zhang Y (2020) Etiology and molecular-epidemiological characteristics of viral meningo-encephalitis in Zhejiang province, 2002–2018. Zhonghua Liuxingbingxue Zazhi 41:562

    CAS  PubMed  Google Scholar 

  21. 21.

    Chen X, Li J, Guo J, Xu W, Sun S, Xie Z (2017) An outbreak of echovirus 18 encephalitis/meningitis in children in Hebei Province, China, 2015. Emerg Microbes Infect 6:1–3

    PubMed Central  Google Scholar 

  22. 22.

    Li W, Qiong Z, Xiao-Ting S, Yu-Jie L, Jian-Hua M, Qiang S, Shi-Qiang S (2016) Molecular epidemiological study of enteroviruses associated with encephalitis in children from Hangzhou, China. Medicine 95:e4870

    Article  Google Scholar 

  23. 23.

    Chen X, Ji T, Guo J, Wang W, Xu W, Xie Z (2019) Molecular epidemiology of echovirus 18 circulating in mainland China from 2015 to 2016. Virol Sin 34:50–58

    CAS  Article  Google Scholar 

  24. 24.

    Lu J, Kang M, Zeng H, Zhong Y, Fang L, Zheng X, Liu L, Yi L, Lin H, Peng J (2020) Tracking echovirus eleven outbreaks in Guangdong, China: a metatranscriptomic, phylogenetic, and epidemiological study. Virus Evol 6:veaa029

    Article  Google Scholar 

Download references


This work was financially supported by the Medical Innovation Team of Jiangsu Province (Grant no. CXTDB2017016) and Top Talent Support Program for young and middle-aged people of Wuxi Health (Grant no. HB2020087).

Author information



Corresponding authors

Correspondence to Jun Qian or Pengwei Zhu.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

This study was approved by the Ethics Committee of the Affiliated Wuxi Children's Hospital of Nanjing Medical University (number: WXCH2019-03-001).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Handling Editor: Zhenhai Chen.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 21 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kang, Y., Hua, Y., Sun, M. et al. A potential new recombinant echovirus 18 strain detected in a 4-year-old child with encephalitis in China in 2019. Arch Virol (2021). https://doi.org/10.1007/s00705-020-04907-w

Download citation